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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.1
- 수록면
- 373 - 378 (6page)
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The nucleotide-binding and oligomerization domain (NOD) is an innate pattern recognition receptor that recognizes pathogen- and damage-associated molecular patterns. The 29-kDa amino-terminal fibronectin fragment (29-kDa FN-f) is a matrix degradation product found in the synovial fluids of patients with osteoarthritis (OA). We investigated whether NOD2 was involved in 29-kDa FN-f-induced pro-catabolic gene expression in human chondrocytes. The expression of mRNA and protein was measured using quantitative real-time polymerase chain reaction (qrt-PCR) and Western blot analysis. Small interfering RNAs were used for knockdown of NOD2 and toll-like receptor 2 (TLR-2). An immunoprecipitation assay was performed to examine protein interactions. The NOD2 levels in human OA cartilage were much higher than in normal cartilage. NOD1 and NOD2 expression, as well as pro-inflammatory cytokines, including interleukin-1beta (IL-1) and tumor necrosis factor-alpha (TNF-), were upregulated by 29-kDa FN-f in human chondrocytes. NOD2 silencing showed that NOD2 was involved in the 29-kDa FN-f-induced expression of TLR-2. Expressions of IL-6, IL-8, matrix metalloproteinase (MMP)-1, -3, and -13 were also suppressed by TLR-2 knockdown. Furthermore, NOD2 and TLR-2 knockdown data demonstrated that both NOD2 and TLR-2 modulated the expressions of their adaptors, receptorinteracting protein 2 (RIP2) and myeloid differentiation 88, in 29-kDa FN-f-treated chondrocytes. 29-kDa FN-f enhanced the interaction of NOD2, RIP2 and transforming growth factor beta-activated kinase 1 (TAK1), an indispensable signaling intermediate in the TLR-2 signaling pathway, and activated nuclear factor-B (NF-B), subsequently leading to increased expressions of pro-inflammatory cytokines and cartilagedegrading enzymes. These results demonstrate that 29-kDa FN-f modulated pro-catabolic responses via cross-regulation of NOD2 and TLR-2 signaling pathways.
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참고문헌 (36)
참고문헌 신청
Felson DT / 2006 / Clinical practice. Osteoarthritis of the knee / N Engl J Med 354:841~848
Goldring MB / 2000 / The role of the chondrocyte in osteoarthritis / Arthritis Rheum 43:1916~1926
Kim HA / 2006 / The catabolic pathway mediated by Toll-like receptors in human osteoarthritic chondrocytes / Arthritis Rheum 54:2152~2163
Xie DL / 1992 / Fibronectin fragments in osteoarthritic synovial fluid / J Rheumatol 19:1448~1452
Homandberg GA / 1996 / Association of proteoglycan degradation with catabolic cytokine and stromelysin release from cartilage cultured with fibronectin fragments / Arch Biochem Biophys 334:325~331
Goldring MB / 2000 / The role of the chondrocyte in osteoarthritis / Arthritis Rheum 43:1916~1926
Kim HA / 2006 / The catabolic pathway mediated by Toll-like receptors in human osteoarthritic chondrocytes / Arthritis Rheum 54:2152~2163
Xie DL / 1992 / Fibronectin fragments in osteoarthritic synovial fluid / J Rheumatol 19:1448~1452
Homandberg GA / 1996 / Association of proteoglycan degradation with catabolic cytokine and stromelysin release from cartilage cultured with fibronectin fragments / Arch Biochem Biophys 334:325~331
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